N. meningitidis is a non-motile, Gram-negative human pathogen that colonises the pharynx and causes meningitis (and, occasionally, septicaemia in the absence of meningitis). It causes both endemic and epidemic disease. Following the introduction of the conjugate vaccine against Haemophilus influenzae type B (Hib), N. meningitidis is the major cause of bacterial meningitis in the USA. A third pathogen responsible for bacterial meningitis is Streptococcus pneumoniae, but an effective vaccine (PrevNar™ [1]) is now available. Like the Hib vaccine, the pneumococcal vaccine is based on conjugated capsular saccharide antigens.
Based on the organism's capsular polysaccharide, various serogroups of N. meningitidis have been identified, including (A, B, C, H, I, K, L, 29E, W135, X, Y & Z. Serogroup A is the pathogen most often implicated in epidemic disease in sub-Saharan Africa. Serogroups B and C are responsible for the vast majority of cases in the United States and in most developed countries. Serogroups W135 and Y are responsible for the rest of the cases in the USA and developed countries. Although the capsular polysaccharide is an effective protective immunogen, each serogroup requires a separate saccharide antigen, and this approach is unsuitable for immunising against serogroup B. Thus the recent success with conjugated saccharide vaccines against serogroup C (Menjugate™ [2], Meningitec™ and NeisVac-C™) has had no impact disease caused by serogroups A, B, W135 or Y; on the contrary, they present a selective pressure towards the emergence of these serogroups as major causes of meningococcal disease.
An injectable tetravalent vaccine of capsular polysaccharides from serogroups A, C, Y & W135 has been known for many years [3,4] and is licensed for human use. The polysaccharides in this vaccine are unconjugated and are present at a 1:1:1:1 weight ratio [5], with 50 μg of each purified polysaccharide. Although effective in adolescents and adults, it induces a poor immune response and short duration of protection and cannot be used in infants [e.g. ref. 6]. Furthermore, the vaccines suffer from the disadvantage of requiring reconstitution from lyophilised forms at the time of use.
For serogroup B, a vaccine has proved elusive. Vaccines based on outer-membrane vesicles have been tested [e.g. ref. 7], but protection is typically restricted to the strain used to make the vaccine.
Thus there remains a need for a vaccine which protects against meningococcal serogroups A, C, W135 and Y in children, and also one which does not require reconstitution prior to administration. Furthermore, there remains a need for a vaccine which broadly protects against serogroup B.